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Considering a patient's weight might improve aspirin dosing in primary prevention against cardiovascular events and make aspirin effective at preventing stroke in men, a meta-analysis suggested.

Low doses of aspirin (75-100 mg) were less effective at reducing cardiovascular events with increasing weight (P=0.0072 for interaction). For instance, these low doses were associated with fewer events for people weighing 110.2-152.1 lbs (50-69 kg, HR 0.75, 95% CI 0.65 to 0.85) -- but not those 154.3 lbs (70 kg) or more (HR 0.95, 95% CI 0.86 to 1.04), according to Peter Rothwell, MD, PhD, of the University of Oxford, John Radcliffe Hospital, in England, and colleagues.

Moreover, the difference in stroke rates between the sexes was no longer detectable when body weight was considered, Rothwell's group reported online in .

Heavier people who did suffer a cardiovascular event were more likely to have died from it if they were on low-dose aspirin (OR 1.33, 95% CI 1.08 to 1.64). On the other hand, higher-dose aspirin was only associated with reduced cardiovascular events for those in a higher weight class (P=0.017 for interaction).

Taking too much aspirin not only didn't work for some people, but was also associated with harm: The risk of sudden death was increased by aspirin in people at low weight for dose (P=0.0018 for interaction), and deaths were more common in people weighing <50 kg taking aspirin at even 75-100 mg (HR 1.52, 95% CI 1.04 to 2.21).

"In conclusion, the optimal dose of aspirin to prevent cardiovascular events depends on body weight, driven more by lean body mass and height than by BMI," the authors said.

"That 75-100 mg aspirin was ineffective in primary prevention of cardiovascular events in the 80% of men and nearly 50% of women who weighed 70 kg [154.3 lbs] or more in our study, even increasing the case fatality of first events, questions the use of once-daily low doses of aspirin irrespective of weight."

Other Implications for Practice

Other implications for practice, Rothwell and colleagues said, are that comparisons of aspirin with other antiplatelet or antithrombotic regimens should be stratified by body size, and that interactions between dose and weight probably explain why men don't appear to derive preventive benefit from aspirin for stroke and myocardial infarction even after accounting for body mass index.

Weight-adjusted dosing would result in increased daily doses of aspirin in the majority of patients, which would be expected to affect bleeding risk, wrote Katherine Theken, PharmD, PhD, and Tilo Grosser, MD, of Perelman School of Medicine of the University of Pennsylvania in Philadelphia, in an accompanying .

"Rothwell and colleagues present provocative results with the potential to substantially affect public health. Clearly, further research is warranted to establish whether weight-adjusted dosing of aspirin should be incorporated into clinical care."

For the meta-analysis, the investigators pooled patient-level data from 10 trials (n=117,279) in which the median weights of study participants ranged from 60.0 to 81.2 kg (132.3 to 179.0 lbs, P<0.0001).

Optimal aspirin dosing for colorectal cancer prevention also depended on weight (P=0.038 for interaction), the investigators said. Low-dose aspirin was tied to lower cancer risk in patients weighing less than 70 kg (154.3 lbs, HR 0.64, 95% CI 0.50 to 0.82) but not in heavier people (HR 0.87, 95% CI 0.71 to 1.07).

Additionally, the increased bleeding risk associated with taking low-dose aspirin was lost in people weighing 90 kg (198.4 lbs) or more (P=0.024 for interaction).

"Given that aspirin's effects on other outcomes, including cancer, also showed interactions with body size, a one-dose-fits-all approach to aspirin is unlikely to be optimal, and a more tailored strategy is required," Rothwell's group concluded.

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